Inhaled ethylene oxide induces preneoplastic foci in rat liver

The metabolite of E, EO, has been shown to be an extrahepatic carcinogen in rats in long-term studies. By means of a rat liver foci bioassay with 3 to 4 days old Sprague-Dawley rats, EO showed an initiating capacity in the livers of female, but not of male rats, measured as incidence of foci deficient in ATPase. After inhalation of 55 and 100 ppm EO, 8 h daily, 5 days weekly, and over 3 weeks, 1 week of pause, and another 8 weeks of promotion with polychlorinated biphenyls, foci incidence was generally low. But it was concentration dependently higher than in controls 12 weeks after starting the experiment. A linear concentration-effect relationship existed with a correlation coefficient of r = 0.991. With 33 ppm EO the number of foci was not enhanced significantly. The administration of 10,000 ppm E did not result in an enhanced foci incidence. In general the carcinogenic potential of EO, which has not been shown so far to cause hepatic tumors in rats, could be demonstrated in rat liver using a sensitive rat liver foci bioassay.